AI Article Synopsis
- Gravity and electrostatics significantly influence how model cell membranes interact with self-assembled aggregates of dendrimers and phospholipids, which can be important for drug delivery systems.
- Experimental methods, like neutron reflectometry, showed that macromolecule movement across membranes happens only when membranes are elevated above a liquid surface and possess a strong negative charge.
- The findings highlight the potential to manipulate these interactions to enhance targeted drug delivery by adjusting the aggregate charge to activate specific cellular uptake pathways.
Article Abstract
We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow diffusion and continuous delivery. Neutron reflectometry measurements were carried out on supported lipid bilayers of varying charge and on hydrophilic silica surfaces. Translocation of the macromolecule across the membrane and adsorption of the lamellar aggregates occur only when the membrane (1) is located above the bulk liquid and (2) has sufficient negative charge. The impact of such dramatic directionality effects due to bulk phase separation and gravity is emphasized for future biochemical investigations. Further, the potential to switch on the interaction mechanism through tuning the charge of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/mz400551h | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
Bioconjug Chem
January 2025
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-5127, United States.
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.
View Article and Find Full Text PDFSurface-Sensitive Waveguide Imaging for In Situ Analysis of Membrane Protein Binding Kinetics.
Anal Chem
January 2025
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Ligand binding to membrane proteins initiates numerous therapeutic processes. Surface plasmon resonance (SPR), a popular method for analyzing molecular interactions, has emerged as a promising tool for in situ determination of membrane protein binding kinetics owing to its label-free detection, high surface sensitivity, and resistance to intracellular interference. However, the excitation of SPR relies on noble metal films, typically gold, which are biologically incompatible and can cause fluorescence quenching.
View Article and Find Full Text PDFBabesiosis and Sickle Red blood Cells: Loss of Deformability, Heightened Osmotic fragility, and Hypervesiculation.
Blood
January 2025
New York Blood Center, New York, New York, United States.
Babesiosis in sickle cell disease (SCD) is marked by severe anemia but the underlying red blood cell (RBC) rheological parameters remain largely undefined. Here, we describe altered RBC deformability from both primary (host RBC sickle hemoglobin mediated) and secondary changes (Babesia parasite infection mediated) to the RBC membrane using wild type AA, sickle trait AS and sickle SS RBCs. Our ektacytometry (LORRCA) analysis demonstrates that the changes in the host RBC bio-mechanical properties, pre- and post- Babesia infection, reside on a spectrum of severity, with wild type infected AA cells, despite showing a significant reduction of deformability under both shear and osmolarity gradients, exhibiting only a mild phenotype; compared to infected AS RBCs which show median changes in deformability and infected SS RBCs which exhibit the most dramatic impact of infection on cellular rheology, including an increase in Point of Sickling values.
View Article and Find Full Text PDF14-3-3 promotes sarcolemmal expression of cardiac Ca1.2 and nucleates isoproterenol-triggered channel superclustering.
Proc Natl Acad Sci U S A
February 2025
Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616.
The L-type Ca channel (Ca1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca flux that drives Ca-induced-Ca-release, Ca1.
View Article and Find Full Text PDFProtozoa-enhanced conjugation frequency alters the dissemination of soil antibiotic resistance.
ISME J
January 2025
State Key Laboratory for Ecological Security of Regions and Cities, Ningbo Urban Environment Observation and Research Station, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China.
Protozoa, as primary predators of soil bacteria, represent an overlooked natural driver in the dissemination of antibiotic resistance genes. However, the effects of protozoan predation on antibiotic resistance genes dissemination at the community level, along with the underlying mechanisms, remain unclear. Here we used fluorescence-activated cell sorting, qPCR, combined with metagenomics and reverse transcription quantitative PCR, to unveil how protozoa (Colpoda steinii and Acanthamoeba castellanii) influence the plasmid-mediated transfer of antibiotic resistance genes to soil microbial communities.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!